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1.
J Neurosurg Case Lessons ; 7(10)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38437676

RESUMO

BACKGROUND: Bifocal germ cell tumors, with primarily identical tissue composition, occur concurrently in the neurohypophyseal and pineal regions. OBSERVATIONS: A 16-year-old male patient exhibited increased intracranial pressure symptoms, with concurrent tumors in the pineal and neurohypophyseal regions, causing obstructive hydrocephalus. His serum human chorionic gonadotropin level was elevated, measuring 506.6 mIU/mL. Upon gross endoscopic examination, the pineal tumor appeared white, whereas the neurohypophyseal tumor appeared red and hemorrhagic. Because of the limited sample size of the latter, a frozen section biopsy was feasible only for the pineal lesion, which indicated the presence of a germinoma. Subsequently, carboplatin and etoposide were administered, resulting in the reduction of the pineal tumor, but no effect was observed in the neurohypophyseal tumor. Histopathological analysis confirmed the pineal lesion as a germinoma, whereas the neurohypophyseal lesion was an embryonal carcinoma. Thus, the treatment was altered to ifosfamide, carboplatin, and etoposide (ICE), leading to a response in both tumors. The patient underwent three additional cycles of ICE therapy and high-dose chemotherapy, followed by whole craniospinal irradiation, achieving complete remission. LESSONS: Although most bifocal germ cell tumors share the same histological tissue, occasional differences may arise, necessitating separate biopsies for accurate assessment.

2.
Comp Immunol Microbiol Infect Dis ; 73: 101540, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32911379

RESUMO

Rhodococcus equi causes suppurative pneumonia in foals aged 1-3 months; moreover, it has emerged as a pathogenic cause of zoonotic diseases. After the initial report of the ruminant-pathogenic factor VapN encoded by the novel virulence plasmid pVAPN, several reports have described ruminant infections caused by vapN-harboring R. equi. Herein, we conducted a serological epidemiological surveillance in goats at a breeding farm (Farm A) and characterized the vapN-harboring R. equi isolates from this farm. First, we established a simple screening enzyme-linked immunosorbent assay (ELISA) using recombinant glutathione S-transferase-tagged VapN as an immobilized antigen. This method revealed that the VapN antibody titers were elevated in 12 of 42 goats. Subsequently, we attempted to isolate R. equi from the goat feces and soil of Farm A. choE+/vapN+R. equi was isolated from the feces of Goat No. 27 and a soil sample near the shed. The pulsed-field gel electrophoresis (PFGE) patterns of five vapN-harboring R. equi strains isolated from Farm A in 2013 and 2019 were investigated and found to be the same except for the strain (OKI2019F1). However, no difference was observed in VapN expression and growth in macrophages among these vapN-harboring R. equi isolates. Our results revealed that some goats had histories of vapN-harboring R. equi infections, and two genomic types of vapN-harboring R. equi were found in isolates from Farm A. Ruminant-specific (pVAPN-carrying) R. equi might be an unrecognized pathogen in Japan and further studies are required to determine its prevalence and distribution.


Assuntos
Infecções por Actinomycetales/veterinária , Doenças das Cabras/epidemiologia , Rhodococcus equi/imunologia , Rhodococcus/imunologia , Infecções por Actinomycetales/epidemiologia , Animais , Anticorpos Antibacterianos/sangue , Bovinos , Doenças dos Bovinos/microbiologia , Feminino , Doenças das Cabras/microbiologia , Cabras , Japão , Rhodococcus equi/genética
3.
Arch Virol ; 154(5): 775-81, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19343474

RESUMO

Feline infectious peritonitis (FIP) is a feline coronavirus (FCoV)-induced fatal disease of domestic and wild cats. The infiltration of neutrophils into granulomatous lesions is unusual for a viral disease, but it is a typical finding of FIP. This study aimed to investigate the reason for the lesions containing neutrophils in cats with FIP. Neutrophils of cats with FIP were cultured, and changes in the cell survival rate were assessed. In addition, the presence or absence of neutrophil survival factors was investigated in specimens collected from cats with FIP. Furthermore, it was investigated whether macrophages, one of the target cells of FIPV infection, produce neutrophil survival factors (TNF-alpha, GM-CSF, and G-CSF). We showed that virus-infected macrophages overproduce neutrophil survival factors, and these factors act on neutrophils and up-regulate their survival. These observations suggest that sustained production of neutrophil survival factors by macrophages during FCoV infection is sufficient for neutrophil survival and contributes to development of granulomatous lesions.


Assuntos
Coronavirus Felino/imunologia , Peritonite Infecciosa Felina/imunologia , Macrófagos/imunologia , Neutrófilos/imunologia , Animais , Gatos , Células Cultivadas , Coronavirus Felino/patogenicidade , Expressão Gênica , Fator Estimulador de Colônias de Granulócitos/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Granuloma/imunologia , Granuloma/virologia , Macrófagos/metabolismo , Macrófagos/virologia , Neutrófilos/virologia , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/imunologia
4.
Bioorg Med Chem Lett ; 18(17): 4849-52, 2008 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-18701284

RESUMO

We describe herein the synthesis and biological evaluation of a series of novel cephalosporins with potent activity against Pseudomonas aeruginosa. Introduction of various amino groups to the 4-position of a 3-amino-2-methylpyrazole cephalosporin 3-side chain resulted in enhanced MIC values against multiple Pseudomonas aeruginosa strains and ultimately led to the discovery of FR264205 (15) with excellent anti-bacterial activity and weak convulsion effect by direct intracerebroventricular injection assay.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Cefalosporinas/síntese química , Cefalosporinas/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Animais , Antibacterianos/efeitos adversos , Antibacterianos/química , Ceftazidima/farmacologia , Cefalosporinas/efeitos adversos , Cefalosporinas/química , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Camundongos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Convulsões/induzido quimicamente , Relação Estrutura-Atividade
5.
Bioorg Med Chem ; 16(5): 2261-75, 2008 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-18082409

RESUMO

AmpC beta-lactamase is one of the leading causes of Pseudomonas aeruginosa (P. aeruginosa) resistance to cephalosporins. FR259647 is a cephalosporin having a novel pyrazolium substituent at the 3-position and exhibits excellent activity (MIC=1 microg/mL) against the AmpC beta-lactamase overproducing P. aeruginosa FP1380 strain in comparison with the third-generation cephalosporins FK518 [Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 454; Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 455; Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 456; Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 457] (MIC=16 microg/mL) and ceftazidime (CAZ) (MIC=128 microg/mL). The stability of FR259647 and FK518 to AmpC beta-lactamase was evaluated using MIC assays against both the P. aeruginosa PAO1 strain and a PAO1 mutant strain overproducing AmpC beta-lactamase as a differential assay, which indicates that the main difference derives from their stability to AmpC beta-lactamase. A structural analysis using computer simulations indicated that the difference in stability may be due to steric hindrance of the 3-position substituents causing differential affinity. This steric hindrance may disturb entry of the cephalosporins into the binding pocket. We predicted the possibility of inhibition of entry as a potential means of enhancing stability by conformational analysis. In order to validate this speculation, novel FR259647 derivatives 4-9 were designed, calculated, synthesized, and evaluated. As a result, we demonstrated that their probability of entry correlated with the MIC ratio of the mutant strain to the parent strain and supports the validity of our model.


Assuntos
Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Cefalosporinas/química , Cefalosporinas/farmacologia , Inibidores de beta-Lactamases , beta-Lactamases/metabolismo , Proteínas de Bactérias/química , Estabilidade Enzimática/efeitos dos fármacos , Imageamento Tridimensional , Modelos Moleculares , Estrutura Molecular , Ligação Proteica , Pseudomonas aeruginosa/efeitos dos fármacos , Resistência beta-Lactâmica/efeitos dos fármacos , beta-Lactamases/química
6.
Virology ; 364(1): 64-72, 2007 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-17382365

RESUMO

The pathogenicity of feline infectious peritonitis virus (FIPV) is known to depend on macrophage tropism, and this macrophage infection is enhanced by mediation via anti-S antibody (antibody-dependent enhancement, ADE). In this study, we found that TNF-alpha production was increased with viral replication in macrophages inoculated with a mixture of FIPV and anti-S antibody, and demonstrated that this culture supernatant had feline PBMC apoptosis-inducing activity. We also demonstrated that the expression level of the FIPV virus receptor, feline aminopeptidase N (fAPN), was increased in macrophages of FIP cats. For upregulation of TNF-alpha and fAPN in macrophages, viral replication in macrophages is necessary, and their expressions were increased by ADE of FIPV infection. It was demonstrated that a heat-resistant fAPN-inducing factor was present in the culture supernatant of FIPV-infected macrophages, and this factor was TNF-alpha: fAPN expression was upregulated in recombinant feline TNF-alpha-treated macrophages, and FIPV infectivity was increased in these macrophages. These findings suggested that FIPV replication in macrophages increases TNF-alpha production in macrophages, and the produced TNF-alpha acts and upregulates fAPN expression, increasing FIPV sensitivity.


Assuntos
Antígenos CD13/metabolismo , Coronavirus Felino/patogenicidade , Macrófagos/imunologia , Macrófagos/virologia , Receptores Virais/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Animais , Apoptose , Sequência de Bases , Gatos , Células Cultivadas , Coronavirus Felino/genética , Coronavirus Felino/fisiologia , Meios de Cultivo Condicionados , Primers do DNA/genética , Peritonite Infecciosa Felina/genética , Peritonite Infecciosa Felina/imunologia , Peritonite Infecciosa Felina/metabolismo , Peritonite Infecciosa Felina/virologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/enzimologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , Receptores Virais/genética , Proteínas Recombinantes/farmacologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/farmacologia , Regulação para Cima , Replicação Viral/efeitos dos fármacos
7.
J Org Chem ; 67(4): 1359-67, 2002 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-11846687

RESUMO

A general and efficient synthesis of allenes using a palladium(0)/diethylzinc system is described. Treatment of mesylates or trichloroacetates of (E)- or (Z)-2-bromoalk-2-en-1-ols with diethylzinc in the presence of a catalytic amount of palladium(0) affords allenes bearing an aminoalkyl, alkyl, or aryl substituent(s) in good to high yields. No transfer of chirality from the stereogenic center carrying the mesyloxy group to the allene was observed.

9.
J Org Chem ; 63(20): 7053-7061, 1998 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-11672331

RESUMO

Although reactions of 2,3-trans-N-arylsulfonyl-3-alkyl-2-alkenylaziridines with organocopper reagents give a mixture of two or three products, the corresponding 2,3-cis-isomers provide a highly efficient route to synthetically important nonracemic (E)-allylamines. It is also found that the reaction proceeds via the well-known anti-S(N)2' pathway.

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